Posttranscriptional Regulation of Nrf2 Through miRNAs and their Role in Alzheimer's Disease

Abstract The nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/Nrf2) is a pivotal facilitator of cytoprotective responses against the oxidative/electrophilic insults. Upon activation, Nrf2 induces transcription of a wide range of cytoprotective genes containing the antioxidant response element (ARE) in their promoters. Dysfunction in Nrf2 signaling has been linked to the pathogenesis of AD and several studies have suggested that boosting Nrf2 expression/activity by genetic or pharmacological approaches is beneficial in AD. Among the diverse mechanisms that regulate the Nrf2 signaling, miRNAs-mediated regulation of Nrf2 has gained much attention in recent years. Several miRNAs have been reported to directly repress the post-transcriptional expression of Nrf2 and thereby negatively regulate the Nrf2-dependent cellular cytoprotective response in AD. Moreover, several Nrf2 targeting miRNAs are misregulated in AD brains. This review is focused on the role of misregulated miRNAs that directly target Nrf2, in AD pathophysiology. Here, alongside a general description of functional interactions between miRNAs and Nrf2, we will review the evidence indicating the possible role of these miRNAs in AD pathogenesis.